This invention relates to the use of CRF antagonists in the treatment of certain conditions, and related compositions.
CRF antagonists are disclosed in U.S. Pat. Nos. 4,605,642 (Issued Aug. 12, 1986) and 5,063,245 (issued Nov. 5, 1991). They are also disclosed in International patent publications WO 95/33750 (published Dec. 14, 1995); WO 95/34563 (published Dec. 21, 1995); WO 94/13676 (published Jun. 23, 1994); WO 94/13677 (published Jun. 23, 1994); WO 95/33727 (published Dec. 14, 1995); WO 98/05661 (published Feb. 12, 1998); WO 98/08847 (published Mar. 5, 1998); and WO 98/08846 (published Mar. 5, 1998) and European patent publications EP 778277 (published Jun. 11, 1997) and EP 773023 (published May 14, 1997). CRF antagonists are also disclosed in the following patent publications: EP 576350; WO 95/10506 (published Apr. 20, 1995); WO 96/35689 (published Nov. 14, 1996); WO 96/39400 (published Dec. 12, 1996); WO 97/00868 (published Jan. 9, 1997); WO 97/14684 (published Apr. 24, 1997); WO 97/29109 (published Aug. 14, 1997); WO 97/29110 (published Aug. 14, 1997); WO 97/35580 (published Oct. 2, 1997); WO 97/35846 (published Oct. 2, 1997), WO 97/44038 (published Nov.27, 1997); WO 98/03510 (published Jan. 29, 1998); WO 98/08821 (published Mar. 5, 1998); WO 98/11075 (published Mar. 19, 1998), WO 98/15543 (published Apr. 16, 1998); WO 98/21200 (published May 22, 1998); WO 98/27066 (published Jun. 25, 1998); WO 98/29397 (published Jul. 9, 1998); WO 98/29413 (published Jul. 9, 1998); WO 98/42699 (published Oct. 1, 1998); WO 98/35967 (published Aug. 20, 1998); WO 98/45295 (published Oct. 15, 1998); WO 98/47874 (published Oct. 29, 1998); WO 98/47903 (published Oct. 29, 1998); WO 99/01454 (published Jan. 14, 1999); WO 99/01439 (published Jan. 14, 1999); WO 99/10350 (published Mar. 4, 1999); WO 99/12908 (published Mar. 18, 1999); WO 99/00373 (published Jan. 7, 1999); and WO 99/38868 (published Aug. 5, 1999).
The importance of CRF antagonists is set out in the literature, e.g., P. Black, Scientific American SCIENCE and MEDICINE,1995, p. 16-25; T. Lovenberg, et al., Current Pharmaceutical Design, 1995, 1: 305-316; and U.S. Pat. No. 5,063,245. An outline of the activities possessed by CRF antagonists is found in M. J. Owens et al., 1991, Pharm. Rev., 43:425-473. CRF antagonists are described in the art as being effective in the treatment of stress-related illnesses, mood disorders such as depression, major depressive disorder, single episode depression, recurrent depression, child abuse induced depression, postpartum depression, dysthemia, bipolar disorders, and cyclothymia; chronic fatigue syndrome; eating disorders such as anorexia and bulimia nervosa; generalized anxiety disorder; panic disorder; phobias, obsessive-compulsive disorder; post-traumatic stress disorder; pain perception such as fibromyalgia; headache; gastrointestinal diseases; hemorrhagic stress; ulcers; stress-induced psychotic episodes; fever; diarrhea; post-operative ileus; colonic hypersensitivity, irritable bowel syndrome; Crohn""s disease; spastic colon; inflammatory disorders such as rheumatoid arthritis and osteoarthritis; pain; asthma; psoriasis; allergies; osteoporosis; premature birth; hypertension, congestive heart failure; sleep disorders; neurodegenerative diseases such as Alzheimer""s disease, senile dementia of the Alzheimer""s type, multiinfarct dementia, Parkinson""s disease, and Huntington""s disease; head trauma; ischemic neuronal damage; excitotoxic neuronal damage; epilepsy; stroke; spinal cord trauma; psychosocial dwarfism; euthyroid sick syndrome; syndrome of inappropriate antidiarrhetic hormone; obesity; chemical dependencies and addictions; drug and alcohol withdrawal symptoms; infertility; cancer; muscular spasms; urinary incontinence; hypoglycemia and immune dysfunctions including stress induced immune dysfunctions, immune suppression and human immunodeficiency virus infections; and stress-induced infections in humans and animals.
The present invention relates to a method of treating a condition comprising administering a corticotropin releasing factor (CRF) antagonist in an amount effective to treat the condition, the condition being selected from the group consisting of:
a) disorders that can be treated by altering circadian rhythm; and
b) depression, further wherein a second compound for treating depression is administered, the second compound for treating depression having an onset of action that is delayed with respect to that of the CRF antagonist.
In another aspect, the present invention relates to a method for treating or preventing a cardiovascular disease that involves administering a CRF antagonist in combination with a non-CRF antagonist compound for treating the disease. The invention also relates to treatment of migraine or non-migraine headache by administration of a CRF antagonist in combination with a non-CRF antagonist compound that treats such condition and to treatment of emesis using a CRF antagonist in combination with a non-CRF antagonist compound for treating emesis.